HCC, an occasional outcome of chronic infection with hepatitis B or C viruses (HBV, HCV) in humans, has been described in only three chimpanzees. HCC and adjacent nontumorous liver from autopsies from two of these were studied using an avidin-biotin-complex immunohistochemical method. Both tumors were well-differentiated trabecular HCCs. Neither chimpanzee had active HBV infection; one had chronic non-A, non-B hepatitis (most likely due to HCV). TGF-alpha stained strongly in >70% of HCC cells of both chimpanzees (most other HCC cells were negative). The HCCs of both chimpanzees stained negatively for p53; this probably indicates the absence of mutant p53 protein. However, one chimpanzee had several microscopic foci of hepatocytes in the nontumorous liver that contained a few nuclei (<1%) that stained positively for p53, possibly the result of additional mutational events outside the tumor. Oval cells, characterized by oval nuclei, clear and scanty cytoplasm, and dimensions that are smaller than mature hepatocytes, were observed in liver tissues from both chimpanzees in the present study and were stained strongly positive for TGF-alpha.